Dementia Flashcards
dementia
syndrome that may be caused by a number of illnesses in which there is a progressive decline in multiple areas of functioning
dementia symptoms
decline in memory and reasoning
decline in communication skills
inability to carry out daily activities
agitation
aggression
wandering
shouting
repeated questioning
sleep disturbance
depression and psychosis
most common type of dementia
Alzheimer’s
dementia types
alzheimers
vascular
Lewy body
frontal temporal
parkinsin
mixed
does alzheimers or vascular dementia progress more quickly
vascular
dementia risk factors
age
genetics+ family hx
down syndrome
high cholesterol
hypertension
diabetes
cognitive inactivity/ low educational attainment
head injury
depression
why can education, sodoku, and novel reading be protective against dementia
mental challenge
2 key features of dementia in the brain
amyloid plaques
Tau tangles
where are amyloid plaques found
between neurones and in cerebral vessels
where are tau tangles found
neurones
alzeimers disease brain changes
beta amyloid deposits
Tau/neurofibrillary tangles
neuritic dystrophy
synaptic loss
selective neuronal cell loss
loss of ACh cells
do tau tangles or amyloid plaques develop first
amyloid plaques
why are people with downs syndrome at higher risk for dementia
extra copy of APP gene on extra chromosome 21
4 genes involved in alzheimers
APP
PSEN1 -> subunit y secretase
PSEN2 -> subunit y secretase
Apolipoprotein E
where is APP expressed
neurones
glial cells
endothelium
smooth muscle
what protein does the APP gene encode
amyloid precursor protein
3 enzymes that cleave amyloid precursor protein
beta secretase
alpha secretase
gamma secretase
is dementia risk increased by mutations that increase or decrease amyloid beta production
increase
most common cause of early onset AD
PSEN1 mutations
PSEN1 and PSEN2 role in AD
encodes presenilin-1 and presenilin-2 which are subunits of gamma secretase
which secretases are involved in the non amyloidogenic and amyloidogenic pathways of APP processing
non amyloidogenic - alpha and gamma
amyloidogenic - beta and gamma
what decides which isoforms of APP are produced
which secretases are present
amyloidogenic pathway of APP processing
beta secretase cleaves APP -> gamma secretase cleaves APP -> A beta formed -> A beta aggregates and oligomerizes forming plaques
are amyloid plaques always pathological
no, normal physiological process and plaques can be inert and not affect cognition
why does amyloid production increase with age
decreased clearance
overproduction
how do amyloid plaques cause damage
trigger inflammatory response
neuritic injury within plaques
oxidative stress
alters kinase/phosphatase activity
apolipoprotein E
secreted lipoprotein involved in cholesterol metabolism
which APOE isoform is most dangerous and what does it do
ApoE4
decrease beta amyloid clearance
do amyloid plaques or Tau tangles correlate with cognitive decline
tau tangles
why is ACh signalling decreased in AD
increased acetylcholinesesterase
degeneration of ACh pathways
AD treatments
acytylcholinesterase inhibitors
NMDA antagonists
antidepressants
antipsychotics
mood stabilisers
what type of drugs are donepezil, galantamine, and rivastigmine
acetylcholinesterase inhibitors
NMDA receptor antagonist drug
memantine
